Test system and method for flexible containers

ABSTRACT

A portable test device and related method are disclosed for conducting integrity testing of flexible containers. The test is particularly useful for testing aseptic flexible film bags in a manner that maintains the sterile nature of the container and removes crinkles by inflating the containers to remove crinkles and establish an inflation set point. The decay in pressure is measured over a predetermined period of time; if pressure loss does not exceed a predetermined threshold the integrity of the bag is confirmed and it can be filled without further manipulation of the container that may result in introducing flaws.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation of U.S. patent applicationSer. No. 13/974,771, filed Aug. 23, 2013, now U.S. Pat. No. 9,285,291,which is a continuation of U.S. patent application Ser. No. 13/615,935,filed on Sep. 14, 2012, now U.S. Pat. No. 8,534,120, which areincorporated herein by specific reference.

FIELD OF THE INVENTION

This invention relates to flexible containers and more particularly to atest system and method for evaluating the integrity of such containers.

BACKGROUND OF THE INVENTION

Flexible containers are commonly used for containment and delivery ofmedical fluids. These containers are generally single use bagsmanufactured from one or more types of plastic film that can beirradiated or otherwise withstand sterilization such that the containercan be rendered aseptic. The containers are often used in life scienceapplications and in the manufacture of pharmaceuticals to contain liquidraw materials prior to or during manufacture; in other cases suchcontainers may be used to contain the finished product. The contents ofthese containers may be precious, particularly when used in large scaleproduction. It is not unusual for even small containers to containmaterial worth many thousands of dollars.

Accordingly, it is beneficial to try to determine in advance whether thecontainer may have an abnormality that might result in a rupture orother failure of the container that could lead to a loss of itscontents.

One common solution employed for testing container integrity is topartially fill the container with helium, the container being placedwithin an enclosure along with a sensor able to detect the presence ofhelium. If helium is detected, a determination can be made whether thereare any pores or pin holes not readily observable through which thehelium is escaping.

Among the drawbacks to this methodology is that helium testers aregenerally large in size and expensive to operate. These systems requirea ready source of helium that adds further expense and that also limitsthe available locations within a facility where that testing can takeplace. Furthermore, helium testing requires that the container berestrained, which requires additional valuable technician time. Yetanother drawback is that silicon and other materials sometimes used inthe manufacture of flexible containers are permeable to helium, makingleak detection difficult and increasing the likelihood of falsepositives and the chance that a satisfactory bag will be needlesslydiscarded.

Even in situations where the container has no flaws from manufacture,they are shipped in a deflated or even evacuated state for conveniencein shipping and storage. As the containers are filled, they expand as aresult of the incoming fluid being pumped into the container. Filling istypically an automated process set to pump a pre-determined volume offluid corresponding to the size of the container. However, the nature ofthe plastic used to form the containers is such that crinkles or otherareas of self-adhesion may have developed during folding. This canresult in a net decrease in the total volume of the container availablefor storage compared to the manufactured volume.

In many industrial settings, the containers may have a volume of severalhundred or even a thousand or more liters. Thus, the weight of thecontainer during filling can quickly become so heavy that manualmanipulation to eliminate crinkles is impractical or impossible. Insevere cases, the reduction in volume may be such that the volume of theliquid being pumped into the container exceeds the available containervolume as a result of the crinkles to the point that the elasticity ofthe plastic is exceeded and the container bursts.

These and other disadvantages are found in known systems and methods fortesting the integrity of flexible containers.

SUMMARY OF THE INVENTION

Exemplary embodiments provide a testing system and method for evaluatingthe integrity of flexible containers in place, allow for the use of airin conducting the tests that avoids the use of expensive helium testingsystems, and which reduces or eliminates crinkles prior to filling thecontainer with liquid to further reduce the risk of failure duringfilling.

According to an exemplary embodiment of the present disclosure, a methodfor testing the integrity of a flexible container comprises providing adeflated flexible container, inflating the flexible container with asterile gas to reach a predetermined pressure within the flexiblecontainer, monitoring pressure within the flexible container for apredetermined period of time and comparing the pressure of the flexiblecontainer after the predetermined period of time to a predetermined setpoint.

In another embodiment, a portable flexible container integrity testdevice comprises a programmable logic controller (PLC), a pressuretransducer in electronic communication with the PLC, a power sourceconfigured to provide electrical power to the PLC, a blower inelectronic communication with the PLC, a gas delivery pathway inselective fluid communication with the blower, and a human/machineinterface in electronic communication with the PLC. The device isportable and configured to fluidly connect to a flexible container viathe gas delivery pathway.

One advantage of an embodiment of the present disclosure is that heliumtesting systems and their attendant trouble and expense can be avoided.

Yet another advantage of an embodiment of the present disclosure is thatintegrity testing can be performed on flexible containers using ordinaryair.

Another advantage of an embodiment of the present disclosure is that thetesting process is also useful to remove crinkles that may otherwiseresult in container failure during filling.

Yet another advantage of an embodiment of the present disclosure is thata portable device is provided for carrying out the integrity testingwhich decreases handling of the container and thus also decreases thepossibility of introducing flaws that were not previously present.

Still another advantage of an embodiment of the present disclosure isthat the container can be tested for leaks at the same location where itwill be filled, reducing the likelihood that new leaks might beintroduced during transport from the testing site to the filling site.

Other features and advantages of the present invention will be apparentfrom the following more detailed description of the preferredembodiment, taken in conjunction with the accompanying drawings whichillustrate, by way of example, the principles of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view of a test and filling station employing aportable flexible container integrity test device in accordance with anexemplary embodiment.

FIG. 2 is a perspective view of the portable flexible containerintegrity test device in accordance with an exemplary embodiment.

FIG. 3 is a front view of the of the portable flexible containerintegrity test device with the front housing removed for illustration.

FIG. 4 is an exemplary screen view of the portable flexible containerintegrity test device for carrying out the test method in accordancewith exemplary embodiments.

Wherever possible, the same reference numbers will be used throughoutthe drawings to represent the same parts.

DETAILED DESCRIPTION OF THE INVENTION

Provided is a portable test device and related method for conductingintegrity testing of flexible containers and particularly for testingaseptic flexible film bags in a manner that maintains the sterile natureof the container while also overcoming drawbacks experienced withconventional testing and filling techniques.

Turning to FIG. 1, an exemplary embodiment of the invention isschematically illustrated by positioning a portable flexible containerintegrity test device 100 in proximity to a flexible container 200 thatis to be tested and subsequently filled with a liquid. As illustrated,the container 200 is filled by a pump 300, which is preferably aperistaltic pump 300 to permit an aseptic flow of the liquid into thecontainer 200.

The flexible container 200 may be any suitable single-use flexiblecontainer. Generally, the container 200 is originally provided in afolded and deflated and/or evacuated state in the manner it is receivedfrom the manufacturer. The flexible container 200 may be of any size,but the testing methods conducted in accordance with exemplaryembodiments are generally most useful with containers having a volume ofat least 10 L, typically at least 50 L, and in some embodiments in therange of about 100 L to about 5,000 L, such as about 500 L to about3,500 L, for example. The container 200 may likewise be of any geometry,although six-walled containers and other three-dimensional containersare particularly suitable. The geometry and volume of a container 200may depend on the industry in which it will be employed, as well as theparticular purpose for which it is being used. These uses include,without limitation, upstream buffer/media prep, bioreactors, fermenters,harvest, downstream separation and purification, and final productpackaging.

The flexible container 200 can be constructed of any suitable material,which again may depend largely upon the use for which the container willbe employed, but in most cases a single or multi-layer medical gradefilm is preferred. Exemplary materials include high purity U.S.Pharmacopoeia (USP) Class VI films such as polyethylene, ethyl vinylacetate, and polypropylene, all by way of example.

The flexible container 200, initially still in its folded form asreceived from the container manufacturer, is placed inside a tank 400.Any type of tank 400 may be used and is typically constructed of plasticor stainless steel. The tank 400 is generally sized to correspond to theshape and volume of the flexible container 200 when completely filledand provides support for the walls of the container 200 as it expandsupon filling. The tank 400 can also act as a protective carrier that mayallow the container to be transported or shipped after it has beenfilled with fluid.

In some embodiments, the tank 400 may be jacketed for heating or coolingto control the temperature of the liquid contents within the container200. The walls of the tank 400 are generally solid to provide adequatesurface area to support the walls of the container 200, although portsmay be formed in the tank walls to aid in making connections to or fromthe container 200. The side and bottom walls of the tank 400 may alsohave a mesh liner to prevent closing unwanted openings in the container200.

Once placed within the tank 400, the flexible container 200 is inflated,preferably with air. Inflation provides the dual benefit ofpre-inflating the container 200 to remove crinkles that might be presentbefore the heavier liquid is introduced into the container, as well asto assist in testing the integrity of the container 200 to identifypossible leaks that might also lead to a failure when the bag is filled.

Furthermore, inflation and testing can advantageously take place in thesame location as the subsequent filling (i.e., with the containeralready situated within the tank where it will be filled). As previouslymentioned, there is a hazard of introducing damage to the containerassociated with handling, including during placement within the tankwhere it will be filled. Exemplary embodiments provide the additionaladvantage of ensuring container integrity at the point of use, which isnot possible using conventional testing methods. In those cases, thetest occurs at one location and the container is then removed from thetest site, followed by transporting and installing it in the tank at thefilling location, all of which introduce extra handling and thepossibility for damage after the container was already tested.Containers tested in accordance with exemplary embodiments can be testedshortly or even immediately prior to filling and because the handlingsteps of installing the container 200 in the tank 400 occur prior totesting, problems introduced as a result of that handling can beidentified.

According to one exemplary embodiment, the inflation is accomplishedthrough the portable flexible container integrity test device 100, whichcontains a blower 105 and/or is connectable to gas lines that mayalready be running throughout a facility where the container is beingused. In either case, a sterile gas is used to inflate the flexiblecontainer to maintain the aseptic nature of the container 200.Preferably, the gas is air. A filter 150 is placed along a conduit 160that forms part of a gas delivery passage and which connects theflexible container 200 to the portable flexible container integrity testdevice 100. The filter 150 may be either a one-way or a two-way filter.The filter 150 preferably has an average pore size of at least 0.2microns or smaller, which is sufficient to render the air sterile basedon currently accepted standards. As a result, ordinary air canpreferably be used to inflate the container 200 without compromising theaseptic quality of the container's interior.

The container 200 is inflated to a predetermined pressure, which mayvary depending on the materials of construction, i.e., the types offilms used in container manufacture, including the thicknesses of thosefilms and their elasticity. For example, for containers 200 employingpolyethylene as a major constituent and having a thickness in the rangeof about 0.005 in. to about 0.010 in., the container may be inflated toa predetermined pressure set point in the range of about 7 to about 11inches of water column. It will be appreciated however, that such sizesand pressure ranges are exemplary only.

Determining whether the set point pressure has been reached may beaccomplished through the use of any suitable pressure gauge, butpreferably is achieved through the use of a pressure transducer 170connected directly to the container 200 or more preferably indirectly tothe container by being inserted into the gas delivery conduit 160 at alocation adjacent the container 200. This may be advantageous byreducing the number of fittings the container has. The conduit 160 mayadvantageously be configured to connect directly to sampling ports orother standard ports already formed in the flexible container. Thepressure transducer 170 is in electronic communication with aprogrammable logic controller (PLC) 115 as described subsequently inmore detail.

After the set point pressure is reached, the pressure transducer 170measures pressure after a predetermined period of time during which anacceptance test is conducted, which may be referred to as pressuredecay, with some loss of pressure ordinarily occurring over that time.If the pressure stays above a predetermined threshold within thatpredetermined period of time, (i.e., the pressure decay does not reflecta loss low enough to reach the threshold) the integrity of the container200 is confirmed and it can subsequently be filled with the liquid forwhich it was intended. Typically, the pressure is periodically orcontinuously monitored throughout the period set forth for theacceptance test. As a result, if the pressure drops below thepredetermined threshold at any point during the predetermined timeperiod, the integrity of the container 200 may be considered suspect andit can be rejected, removed from the tank 400, and another containerused in its place. All of this can occur prior to filling the container200 with expensive or hazardous liquid contents and the possible wasteof a portion of the same.

The threshold may be selected based on a variety of factors primarilyrelated to the safety factor desired to be incorporated and the level ofassurance that no leaks are present; in some situations a test for grossleaks may be sufficient while in other cases it may be desirable to testfor fine leaks, which may use a lower acceptance set point and/or longertest times. In some cases, the acceptance set point may be between 0.5and 1 inches of water column, more typically in the range of about 0.6to about 0.8 inches of water column. That is, if the pressure drop fromthe inflation set point (or following the rest period as describedbelow) is greater than the threshold, the container 200 is deemed tohave failed the acceptance test. Again it will be appreciated that theidentified set points are exemplary only and that any acceptance setpoint may be employed.

In one embodiment, a pre-determined rest period takes place intermediatethe point at which the inflation set point is reached and the point whenthe acceptance test begins. This rest period provides time for the gasto settle during which crinkles in the container expand so that thecontainer can approach and/or reach its intended volume. This reducesthe likelihood that the net container volume is less than themanufactured volume as a result of the crinkles or other portions thatmay not completely unfold if the bag had not first been inflated priorto filling. Furthermore, the container can be visually inspected duringthis time and can be manually manipulated if significant crinkles areidentified that for whatever reason do not unfold on their own as aresult of the air pressure.

Generally, the rest period can be any desired period of time although arest period of at least 30 seconds and less than about 300 seconds isgenerally preferred to ensure a sufficient rest period is achieved butwithout allowing so much time to pass that results in loss ofefficiency. In some embodiments, the rest period may be in the range of90 to 180 seconds. As with the inflation and acceptance test set points,these rest period times are exemplary only and any time may be selected.

As the container 200 settles and crinkles unfold during the rest period,the volume of the air inside the container 200 increases, which resultsin a corresponding drop in pressure. Accordingly, the pressure againstwhich the acceptance set point is evaluated during the acceptance testis the pressure measured by the pressure transducer at the time the restperiod expires and the acceptance test begins.

Alternatively, in some embodiments, the pressure drop during settlingmay be great enough that it is desirable to recharge the container 200to the inflation set point to expand any additional crinkles that may beleft and/or to raise the pressure within the container 200 to ensurethat meaningful results are obtained during the acceptance test.Generally, if the rest period results in a loss of pressure of more thanabout 30%, it is desirable to recharge the container 200 to theinflation set point prior to conducting the acceptance test.

Whether or not a rest period is employed, the acceptance test may beconducted for any desired period of time, although a test period in therange of 120 to 300 seconds is generally satisfactory, and in oneembodiment, the acceptance test period is about 150 to about 240seconds. Again, these times are exemplary only and any times may beemployed and may vary depending on a variety of factors, including thevolume of the bag under test, as well as the various set points and restperiod employed.

Turning to FIGS. 2 and 3, the portable flexible container integrity testdevice 100 is illustrated in more detail. The device 100 mayconveniently be provided as a self contained unit for ease ofportability, being enclosed within a plastic or stainless steel housing125 supported on casters 135. The device 100 contains the PLC 115 withinthe housing 125. Any suitable controller that is capable of beingprogrammed to receive and process input and measure and respond theretomay be employed as the PLC. A suitable PLC includes those sold under theAllen-Bradley name available from Rockwell Automation. The PLC 115 andother components of the device 100 requiring electrical power may bepowered by a corded connection to a standard A/C outlet. To enhance theportability of the device 100, a battery 145 is preferably containedwith the device housing 125 and used to provide the electric power. Insuch cases, an inverter 155 may also be provided to convert thebattery's direct current to alternating current. Optionally, a chargermay be provided within the housing 125 or otherwise be connectable tothe device 100 so that the battery 145 can be recharged.

The device 100 further includes an internal air passage 165 thattogether with the gas delivery conduit 160 forms the pathway fordelivery of air to inflate the container 200. The internal air passage165 may be constructed from one or more interconnected conduits. Thedevice 100 preferably contains a blower 105. The blower 105 is in fluidcommunication with the container 200 via the internal air passage 165and gas delivery conduit 160. The blower 105 is in electroniccommunication with the PLC 115 that starts and stops the blower 105depending upon whether more air is required in the container 200 toreach the predetermined inflation pressure.

The internal air passage 165 may further be constructed so that insteadof the air being delivered by the blower 105 contained within the devicehousing 125, the device 100 could alternatively be connected to an airnetwork within the facility in which the device is being used. Thiswould permit the device 100 to take advantage of so-called “house air”that would reduce the need for blower operation and save battery life byconnecting the house air to the device 100 by a house air coupling 167.One or more gauges 163 may be employed along the internal air passageway165 to manually monitor the flow of air there through.

A vent 169 may be employed at some point along the air pathway, eitherin the internal air passage 165 or the gas delivery conduit 160, thatcan be opened, for example, should the blower 105 unexpectedly continuerunning after the inflation set point has been reached. This can avoidthe possibility of damaging the container 200 by over-inflation. Thevent 169 can also be used to evacuate air from the container 200 that isdisplaced by liquid during filling operations.

The device 100 further includes the pressure transducer 170, aspreviously described. The pressure transducer 170 is placed within thegas delivery conduit 160 and is in electronic communication with the PLC115 for the measurement and monitoring of air pressure in the container200. Because the pressure transducer 170 is present on the filtered sideof the air sent to the container 200, it should be an aseptic device ifbeing use in an aseptic environment. Preferably, the pressure transducer170 is a sterile, single-use disposable device, such as the pressuretransducers commercially available from Pender-Tech.

The filter 150, pressure transducer 170, and the gas delivery conduit160 are all preferably single-use disposable items for use in asepticenvironments. As a result, these items may conveniently be provided withthe container 200, while the components of the device 100 containedwithin the housing 125 do not need to be maintained in an asepticcondition and thus can be used repeatedly.

A human-machine interface (HMI) 180 provides a user the ability tointeract with and control the portable flexible container integrity testdevice 100 and to cause the test operations to be executed in thedesired manner, adjust set-points, and review results, among otherthings. Preferably, the HMI 180 is a touch screen, although anyinterface and associated input devices (keyboard, mouse, etc.) thatpermit interaction with the PLC 115 may be employed.

Optionally, the device 100 may include a printer and/or a networkconnection to provide output data regarding test results that may belogged and/or linked with the container 200 via a unique identifier forfuture use or reference.

Using the device 100, the container 200 can be inflated and an integritytest performed on it at the point of use in accordance with exemplaryembodiments. This reduces the risk that installation and relatedmanipulation of the empty container 200 will have generated anundetected hole or other flaw; such flaws would have remained undetectedif the container 200 had been tested using conventional testingmethodologies, such as helium testing. Exemplary embodiments also havethe added benefit of reducing or eliminating crinkles that reduce theeffective volume of the container 200 to less than its manufacturedvolume, which can also result in container failure during filling.

FIG. 4 illustrates an exemplary screen shot of the HMI 180 that reflectsthe predetermined inflation set point, acceptance set point, settle time(i.e. rest period) set point, and acceptance test time set point. Itfurther illustrates the device's ability to monitor and graphicallydisplay pressure in real-time, along with other device operationfunctions that can be selected by the touch screen.

Returning to FIG. 1, after the portable flexible container integritytest device 100 has been used to inflate the container 200 and conductthe integrity test, the device 100 can optionally, but advantageously beused as part of the container filling process. The container 200 has afill port 210 that is configured to be coupled to the pump 300. The pump300 is preferably a peristaltic pump which is often used to conveyliquids in aseptic environments.

As a result of the inflation accomplished by the de-crinkling andintegrity testing carried out in accordance with exemplary embodiments,the container 200 has its full or nearly full volume filled by air thatmust be displaced by the incoming liquid. To maintain an asepticenvironment, the container 200 is preferably not vented directly to theatmosphere. Rather the air is directed out through the air passagedelivery conduit in the direction opposite that which it entered. Thismay include passing back through the filter 150 prior to venting so thatany external air that is able to re-enter the container 200 during thefilling process through the vent 169 must pass through the filter 150and thus does not compromise the aseptic environment.

However, the gas delivery conduit 160, particularly with the presence ofthe filter 150 still attached, may have the effect of preventing the airfrom escaping as fast as the liquid is pumped in. This would have theeffect of causing the container 200, formed of a flexible film material,to expand and potentially even to rupture. Accordingly, the portableflexible container integrity test device 100 may remain in electroniccommunication with the pressure transducer 170 during filling, whichallows the device 100 to monitor the inflow of liquid as well as theoutflow of air based on the pressure within the container 200. Theportable flexible container integrity test device 100 can further be inelectronic communication with the pump 300. In the event that themeasured pressure indicates an imbalance between inflow and outflow thatexceeds a predetermined threshold, the device 100 can control the pump300 to reduce the rate at which liquid is being introduced or even topause the pumping until a preset level is reached at which liquid can beintroduced again safely into the container.

While the invention has been described with reference to a preferredembodiment, it will be understood by those skilled in the art thatvarious changes may be made and equivalents may be substituted forelements thereof without departing from the scope of the invention. Inaddition, many modifications may be made to adapt a particular situationor material to the teachings of the invention without departing from theessential scope thereof. Therefore, it is intended that the inventionnot be limited to the particular embodiment disclosed as the best modecontemplated for carrying out this invention, but that the inventionwill include all embodiments falling within the scope of the appendedclaims.

What is claimed is:
 1. A method for integrity testing a flexiblecontainer, the method comprising: inflating a flexible container with agas until a predetermined pressure set point is reached within theflexible container; determining after a first period of time followingthe step of inflating whether the pressure within the flexible containerhas decreased by at least a predetermined amount; reinflating theflexible container until the predetermined pressure set point is reachedwithin the flexible container if it is determined that the pressurewithin the flexible container decreased by at least the predeterminedamount; thereafter measuring a subsequent pressure within the flexiblecontainer after a second period of time; and comparing the measuredsubsequent pressure of the flexible container to a predeterminedthreshold.
 2. The method of claim 1, wherein the flexible container isprovided before inflating as a folded, deflated flexible containersituated in a same tank where the flexible container is subsequentlyfilled with a liquid.
 3. The method of claim 1, wherein the flexiblecontainer is inflated with a sterile gas.
 4. The method of claim 1,wherein the first period of time is in a range of 60 seconds to 240seconds.
 5. The method of claim 4, wherein the second period of time isin a range of 60 seconds to 300 seconds.
 6. The method of claim 1,wherein the steps of inflating, measuring and comparing are accomplishedusing a portable test unit having a blower, a power source, and aprogrammable logic controller contained therein.
 7. The method of claim1, wherein the step of measuring the subsequent pressure within theflexible container is accomplished using a pressure transducer inelectronic communication with the flexible container and a programmablelogic controller.
 8. The method of claim 1, wherein the method furthercomprises filling the flexible container with a liquid after the step ofcomparing.
 9. The method of claim 8, wherein the gas is concurrentlyreleased from the flexible container while the liquid is delivered intothe flexible container, the method further comprising measuring the gaspressure within the flexible container while the gas is being releasedand the liquid is being delivered.
 10. The method of claim 9, furthercomprising adjusting the delivery of the liquid into the flexiblecontainer if the gas pressure within the flexible container exceed apredetermined value.
 11. The method of claim 1, wherein the step ofmeasuring the subsequent pressure within the flexible container furthercomprises monitoring the pressure during the second predetermined periodof time.
 12. The method of claim 11, wherein if the pressure duringmonitoring falls below the predetermined threshold, the flexiblecontainer is rejected.
 13. The method of claim 1, wherein thepredetermined pressure set point is 7 to 11 inches of water column. 14.The method of claim 1, further comprising exhausting at least a portionof the gas from the flexible container through a filter.
 15. The methodof claim 14, further comprising measuring a gas pressure within theflexible container while exhausting the at least a portion of the gasthrough the filter.
 16. The method of claim 1, wherein the flexiblecontainer is reinflated to the predetermined pressure set point if it isdetermined that the pressure within the flexible container is decreasedby at least at least 30%.
 17. The method of claim 1, wherein theflexible container comprises a flexible polymeric bag.